Background: Intensive care patients with nonocclusive mesenteric ischemia (NOMI) show mortality rates of 70% to 90%. Besides emergency surgery, different interventional local vasodilatory treatment (LVT) attempts have been described. We performed a systematic review and a meta-analysis to evaluate feasibility, efficacy, and tolerability of LVT in patients with life-threatening NOMI. Methods: Searches of PubMed, EMBASE, Web of Science, and Cochrane Library databases were performed until February 2019. Measured outcomes included immediate technical success rates (as indicated by mesenteric vasodilation on angiography or clinical improvement) and adverse events (AEs). Therapeutic efficacy was measured by the assessment of overall mortality. Results: Twelve studies (335 patients, 245 received LVT) from 1977 to 2018 were included. All studies were retrospective (4 comparative and 8 noncomparative). Different intra-arterial vasodilators (4× papaverine, 6× prostaglandin E1, 1× tolazoline/heparin, 1× tolazoline + iloprost) were reported. Initial technical success rate was 75.9% (95% confidence interval [CI], 55.1%-89%, P = .017) with an AE rate of 2.9% (95% CI: 1.3%-6.6%; P = .983). Overall mortality in LVT patients was 40.3% (95% CI: 28.7%-53%, P = .134). In 4 studies, outcomes were compared between patients receiving LVT to those who received standard of care (odds ratio for death in LVT patients was 0.261 [95% CI: 0.095-0.712, P = .009]). Conclusions: Local vasodilatory treatment appears to be safe in patients with NOMI and might have the potential to at least partially reverse mesenteric vasoconstriction features in control angiographies. However, with no randomized and prospective studies available yet, the overall quality of published studies has to be considered as low; therefore, it is not possible to draw generalizable conclusions from the present data concerning clinical end points. Its application might hold promise as a rescue treatment strategy and deserves further evaluation in randomized controlled trials.
Background Non-occlusive mesenteric ischemia (NOMI) is a life-threatening condition occurring in patients with shock and is characterized by vasoconstriction of the mesenteric arteries leading to intestinal ischemia and multi-organ failure. Although minimal invasive local intra-arterial infusion of vasodilators into the mesenteric circulation has been suggested as a therapeutic option in NOMI, current knowledge is based on retrospective case series and it remains unclear which patients might benefit. Here, we prospectively analyzed predictors of response to intra-arterial therapy in patients with NOMI. Methods This is a prospective single-center observational study to analyze improvement of ischemia (indicated by reduction of blood lactate > 2 mmol/l from baseline after 24 h, primary endpoint) and 28-day mortality (key secondary endpoint) in patients with NOMI undergoing intra-arterial vasodilatory therapy. Predictors of response to therapy concerning primary and key secondary endpoint were identified using a) clinical parameters as well as b) data from 2D-perfusion angiography and c) experimental biomarkers of intestinal injury. Results A total of 42 patients were included into this study. At inclusion patients had severe shock, indicated by high doses of norepinephrine (NE) (median (interquartile range (IQR)) 0.37 (0.21–0.60) μg/kg/min), elevated lactate concentrations (9.2 (5.2–13) mmol/l) and multi-organ failure. Patients showed a continuous reduction of lactate following intra-arterial prostaglandin infusion (baseline: (9.2 (5.2–13) mmol/l vs. 24 h: 4.4 (2.5–9.1) mmol/l, p < 0.001) with 22 patients (52.4%) reaching a lactate reduction > 2 mmol/l at 24 h following intervention. Initial higher lactate concentrations and lower NE doses at baseline were independent predictors of an improvement of ischemia. 28-day mortality was 59% in patients with a reduction of lactate > 2 mmol/l 24 h after inclusion, while it was 85% in all other patients (hazard ratio 0.409; 95% CI, 0.14–0.631, p = 0.005). Conclusions A reduction of lactate concentrations was observed following implementation of intra-arterial therapy, and lactate reduction was associated with better survival. Our findings concerning outcome predictors in NOMI patients undergoing intra-arterial prostaglandin therapy might help designing a randomized controlled trial to further investigate this therapeutic approach. Trial registration Retrospectively registered on January 22, 2020, at clinicaltrials.gov (REPERFUSE, NCT04235634), https://clinicaltrials.gov/ct2/show/NCT04235634?cond=NOMI&draw=2&rank=1.
Purpose To evaluate the feasibility of 2D-perfusion angiography (2D-PA) for the analysis of intra-procedural treatment response after intra-arterial prostaglandin E1 therapy in patients with non-occlusive mesenteric ischemia (NOMI). Methods Overall, 20 procedures in 18 NOMI patients were included in this retrospective case-control study. To evaluate intra-procedural splanchnic circulation changes, post-processing of digital subtraction angiography (DSA) series was performed. Regions of interest (ROIs) were placed in the superior mesenteric artery (SMA; reference), the portal vein (PV; ROI PV), as well as the aorta next to the origin of the SMA (ROI Aorta). Peak density (PD), time to peak (TTP), and area under the curve (AUC) were assessed, and parametric ratios 'target ROI PD, TTP, AUC /reference ROI' were computed and compared within treatment and control group. Additionally, a NOMI score was assessed pre-and post-treatment compared to 2D-PA. Results Vasodilator therapy leads to a significant decrease of the 2D-PA-derived values PD Aorta (p = 0.04) and AUC Aorta (p = 0.03). These findings correlated with changes of the simplified NOMI score, both for overall (4 to 1, p < 0.0001) and for each category. Prostaglandin application caused a significant increase of the AUC PV (p = 0.04) and TTP PV was accelerated without reaching statistical significance (p = 0.13). When compared to a control group, all 2D-PA values in the NOMI group (pre-and post-intervention) differed significantly (p < 0.05) with longer TTP Aorta/PV and lower AUC Aorta/PV and PD Aorta/PV. Conclusion 2D-PA offers an objective approach to analyze immediate flow and perfusion changes following vasodilatory therapies of NOMI patients and may be a valuable tool for assessing treatment response.
Background: Non-occlusive mesenteric ischemia (NOMI) is a life-threatening condition occurring in patients with shock and is characterized by vasoconstriction of the mesenteric arteries leading to intestinal ischemia and multi-organ failure. Although minimal invasive local intra-arterial infusion of vasodilators into the mesenteric circulation has been suggested as a therapeutic option in NOMI, current knowledge is based on retrospective case series and it remains unclear which patients might benefit. Here, we prospectively analyzed predictors of response to intra-arterial therapy in patients with NOMI.Methods: Prospective single-center observational study to analyze 28-day mortality (primary outcome) and reduction of blood lactate > 2mmol/l from baseline after 24 hours (key secondary endpoint) in patients with NOMI undergoing intra-arterial vasodilatory therapy. Predictors of response to therapy concerning primary and key secondary endpoint were identified using a) clinical parameters as well as b) data from 2D-perfusion angiography and c) experimental biomarkers of intestinal injury.Results: A total of 42 patients were included into this study. At inclusion patients had severe shock, indicated by high doses of norepinephrine (NE) (median (Interquartile Range (IQR)) 0.37 (0.21-0.60) μg/kg/min), elevated lactate concentrations (9.2 (5.2-13) mmol/l), and multi-organ failure. Median intestinal fatty-acid binding protein (i-FABP) (p<0.001) and smooth muscle protein 22 (SM-22) (p<0.0001) plasma concentrations were increased compared to healthy controls indicating significant mucosal and transmural intestinal ischemia at inclusion. 28-day mortality was 71% and higher NE dose and lactate as well as lower thrombocytes, bicarbonate and pH 24 hours following intervention were associated with higher mortality. Patients showed a continuous reduction of lactate following intra-arterial prostaglandin infusion (baseline: (9.2 (5.2-13) mmol/l vs. 24 hours: 4.4 (2.5-9.1) mmol/l, p<0.001). 28-day mortality was 59% in patients with a reduction of lactate > 2 mmol/l 24 hours after inclusion (n=22), while it was 85% in all other patients (n=20) (Hazard Ratio 0.409; 95% CI, 0.14-0.631, p=0.005). Conclusions: A reduction of lactate concentrations was observed following implementation of intra-arterial therapy and lactate reduction was associated with better survival. Our findings concerning outcome predictors in NOMI patients undergoing intra-arterial prostaglandin therapy might help designing a randomized controlled trial to further investigate this therapeutic approach. Trial registration: Retrospectively registered January 22th 2020 at clinicaltrials.gov (REPERFUSE, NCT04235634), https://clinicaltrials.gov/ct2/show/NCT04235634?cond=NOMI&draw=2&rank=1
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